Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells
Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells
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DOI：
10.1038/sj.onc.1206639
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发表时间：
2003-09-11
期刊：
影响因子：
8
通讯作者：
Boxer, LM
中科院分区：
文献类型：
--
作者：
Heckman, CA;Wheeler, MA;Boxer, LM
在伴有t（14;18）易位的滤泡性淋巴瘤中，bcl-2基因表达增加，这依赖于bcl-2 5'侧翼区和免疫球蛋白重链基因增强子内的调节元件。我们发现t（14;18）淋巴瘤表达C/EBPalpha，其通常在B淋巴细胞中不表达。C/EBPalpha的表达增加了bcl-2的表达，并且鉴定了介导这种效应的bcl-2 P2启动子的两个区域。C/EBP β也能够通过这些位点增加bcl-2启动子活性。5'位点富含GC，不含C/EBP共有序列;然而，通过EMSA在体外和通过染色质免疫沉淀测定在体内观察到C/EBP与该位点相互作用。3'区含有Cdx位点，其介导A-Myb对bcl-2启动子的作用。在体内结合研究表明，C/EBP相互作用与此区域的bcl-2启动子以及。由于siRNA分子靶向C/EBP因子的转录物，导致其表达降低，从而导致Bcl-2蛋白的下调。我们的结论是，C/EBPalpha和C/EBPbeta有助于Bcl-2在t（14;18）淋巴瘤细胞中的表达失调。
In follicular lymphomas with the t(14;18) translocation, there is increased expression of the bcl-2 gene, which is dependent upon regulatory elements within the bcl-2 5' flanking region and the immunoglobulin heavy-chain gene enhancers. We found that t(14;18) lymphomas expressed C/EBPalpha, which is not normally expressed in B lymphocytes. Expression of C/EBPalpha increased bcl-2 expression, and two regions of the bcl-2 P2 promoter that mediated this effect were identified. C/EBPbeta was also able to increase bcl-2 promoter activity through these sites. The 5' site was GC-rich and did not contain a C/EBP consensus sequence; however, C/EBP was observed to interact with this site both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay. The 3' region contained the Cdx site, which mediates the effect of A-Myb on the bcl-2 promoter. In vivo binding studies revealed that C/EBP interacted with this region of the bcl-2 promoter as well. Decreased expression of C/EBP factors due to targeting of their transcripts by siRNA molecules resulted in downregulation of Bcl-2 protein. We conclude that C/EBPalpha and C/EBPbeta contribute to the deregulated expression of Bcl-2 in t(14;18) lymphoma cells.